Molecule

Drug Groups

approved

Description

Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It also has been used in the treatment of chronic myeloid leukemia. [Wikipedia]

Indication

For the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.

Pharmacology

Anagrelide is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It works by inhibiting the maturation of megakaryocytes into platelets. The exact mechanism of action is unclear, although it is known to be a potent (IC50 = 36nM) inhibitor of phosphodiesterase-III.

Toxicity

There are no reports of overdosage with anagrelide, however thrombocytopenia, which can potentially cause bleeding, is expected from overdosage. Single oral doses of anagrelide at 2,500, 1,500 and 200 mg/kg in mice, rats and monkeys, respectively, were not lethal. Symptoms of acute toxicity were: decreased motor activity in mice and rats and softened stools and decreased appetite in monkeys.

Affected Organisms

Biotransformation

Extensive, with < 1% recovered unchanged in the urine. Metabolized primarily in the liver by cytochrome P450 1A2 (CYP1A2). Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquinazoline (RL603). Whether these metabolites have biological activities that may underlie the mode of action of the parent drug is presently unclear.

Half Life

At fasting and at a dose of 0.5 mg of anagrelide, the plasma half-life is 1.3 hours.

References

External Links